RESUMO
BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.
RESUMO
OBJECTIVE: This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS: Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS: A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION: MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.
RESUMO
Autoimmune diseases commonly affect various systems, but their etiology and pathogenesis remain unclear. Currently, increasing research has highlighted the role of ferroptosis in immune regulation, with immune cells being a crucial component of the body's immune system. This review provides an overview and discusses the relationship between ferroptosis, programmed cell death in immune cells, and autoimmune diseases. Additionally, it summarizes the role of various key targets of ferroptosis, such as GPX4 and TFR, in immune cell immune responses. Furthermore, the release of multiple molecules, including damage-associated molecular patterns (DAMPs), following cell death by ferroptosis, is examined, as these molecules further influence the differentiation and function of immune cells, thereby affecting the occurrence and progression of autoimmune diseases. Moreover, immune cells secrete immune factors or their metabolites, which also impact the occurrence of ferroptosis in target organs and tissues involved in autoimmune diseases. Iron chelators, chloroquine and its derivatives, antioxidants, chloroquine derivatives, and calreticulin have been demonstrated to be effective in animal studies for certain autoimmune diseases, exerting anti-inflammatory and immunomodulatory effects. Finally, a brief summary and future perspectives on the research of autoimmune diseases are provided, aiming to guide disease treatment strategies.
Assuntos
Doenças Autoimunes , Ferroptose , Ferro , Humanos , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Ferro/metabolismo , Animais , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologiaRESUMO
Objective: To explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. Methods: First, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. Results: The results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). Conclusion: GNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.
RESUMO
Ferroptosis is a form of non-apoptotic regulated cell death (RCD) that depends on iron and is characterized by the accumulation of lipid peroxides to lethal levels. Ferroptosis involves multiple pathways including redox balance, iron regulation, mitochondrial function, and amino acid, lipid, and glycometabolism. Furthermore, various disease-related signaling pathways also play a role in regulating the process of iron oxidation. In recent years, with the emergence of the concept of ferroptosis and the in-depth study of its mechanisms, ferroptosis is closely associated with various biological conditions related to kidney diseases, including kidney organ development, aging, immunity, and cancer. This article reviews the development of the concept of ferroptosis, the mechanisms of ferroptosis (including GSH-GPX4, FSP1-CoQ1, DHODH-CoQ10, GCH1-BH4, and MBOAT1/2 pathways), and the latest research progress on its involvement in kidney diseases. It summarizes research on ferroptosis in kidney diseases within the frameworks of metabolism, reactive oxygen biology, and iron biology. The article introduces key regulatory factors and mechanisms of ferroptosis in kidney diseases, as well as important concepts and major open questions in ferroptosis and related natural compounds. It is hoped that in future research, further breakthroughs can be made in understanding the regulation mechanism of ferroptosis and utilizing ferroptosis to promote treatments for kidney diseases, such as acute kidney injury(AKI), chronic kidney disease (CKD), diabetic nephropathy(DN), and renal cell carcinoma. This paves the way for a new approach to research, prevent, and treat clinical kidney diseases.
Assuntos
Ferroptose , Nefropatias , Ferroptose/efeitos dos fármacos , Humanos , Nefropatias/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Animais , Ferro/metabolismo , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , Terapia de Alvo MolecularRESUMO
INTRODUCTION: Cardiovascular disease nursing is a critical clinical application that necessitates real-time monitoring models. Previous models required the use of multi-lead signals and could not be customized as needed. Traditional methods relied on manually designed supervised algorithms, based on empirical experience, to identify waveform abnormalities and classify diseases, and were incapable of monitoring and alerting abnormalities in individual waveforms. METHODS: This research reconstructed the vector model for arbitrary leads using the phase space-time-delay method, enabling the model to arbitrarily combine signals as needed while possessing adaptive denoising capabilities. After employing automatically constructed machine learning algorithms and designing for rapid convergence, the model can identify abnormalities in individual waveforms and classify diseases, as well as detect and alert on abnormal waveforms. RESULT: Effective noise elimination was achieved, obtaining a higher degree of loss function fitting. After utilizing the algorithm in Section 3.1 to remove noise, the signal-to-noise ratio increased by 8.6%. A clipping algorithm was employed to identify waveforms significantly affected by external factors. Subsequently, a network model established by a generative algorithm was utilized. The accuracy for healthy patients reached 99.2%, while the accuracy for APB was 100%, for LBBB 99.32%, for RBBB 99.1%, and for P-wave peak 98.1%. CONCLUSION: By utilizing a three-dimensional model, detailed variations in electrocardiogram signals associated with different diseases can be observed. The clipping algorithm is effective in identifying perturbed and damaged waveforms. Automated neural networks can classify diseases and patient identities to facilitate precision nursing.
RESUMO
Ischemic stroke (IS) is a major cause of mortality and disability among adults. Recanalization of blood vessels to facilitate timely reperfusion is the primary clinical approach; however, reperfusion itself may trigger cerebral ischemia-reperfusion injury. Emerging evidence strongly implicates the NLRP3 inflammasome as a potential therapeutic target, playing a key role in cerebral ischemia and reperfusion injury. The aberrant expression and function of NLRP3 inflammasome-mediated inflammation in cerebral ischemia have garnered considerable attention as a recent research focus. Accordingly, this review provides a comprehensive summary of the signaling pathways, pathological mechanisms, and intricate interactions involving NLRP3 inflammasomes in cerebral ischemia-reperfusion injury. Moreover, notable progress has been made in investigating the impact of natural plant products (e.g., Proanthocyanidins, methylliensinine, salidroside, α-asarone, acacia, curcumin, morin, ginsenoside Rd, paeoniflorin, breviscapine, sulforaphane, etc.) on regulating cerebral ischemia and reperfusion by modulating the NLRP3 inflammasome and mitigating the release of inflammatory cytokines. These findings aim to present novel insights that could contribute to the prevention and treatment of cerebral ischemia and reperfusion injury.
RESUMO
BACKGROUND: Influenza is an acute respiratory infection caused by influenza virus. Maxing Shigan Decoction (MXSGD) is a commonly used traditional Chinese medicine prescription for the prevention and treatment of influenza. However, its mechanism remains unclear. METHOD: The mice model of influenza A virus pneumonia was established by nasal inoculation. After 3 days of intervention, the lung index was calculated, and the pathological changes of lung tissue were detected by HE staining. Firstly, transcriptomics technology was used to analyze the differential genes and important pathways in mouse lung tissue regulated by MXSGD. Then, real-time fluorescent quantitative PCR (RT-PCR) was used to verify the changes in mRNA expression in lung tissues. Finally, intestinal microbiome and intestinal metabolomics were performed to explore the effect of MXSGD on gut microbiota. RESULTS: The lung inflammatory cell infiltration in the MXSGD group was significantly reduced (p < 0.05). The results of bioinformatics analysis for transcriptomics results show that these genes are mainly involved in inflammatory factors and inflammation-related signal pathways mediated inflammation biological modules, etc. Intestinal microbiome showed that the intestinal flora Actinobacteriota level and Desulfobacterota level increased in MXSGD group, while Planctomycetota in MXSGD group decreased. Metabolites were mainly involved in primary bile acid biosynthesis, thiamine metabolism, etc. This suggests that MXSGD has a microbial-gut-lung axis regulation effect on mice with influenza A virus pneumonia. CONCLUSION: MXSGD may play an anti-inflammatory and immunoregulatory role by regulating intestinal microbiome and intestinal metabolic small molecules, and ultimately play a role in the treatment of influenza A virus pneumonia.
Assuntos
Alphainfluenzavirus , Medicamentos de Ervas Chinesas , Vírus da Influenza A , Influenza Humana , Orthomyxoviridae , Pneumonia , Camundongos , Animais , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Influenza Humana/tratamento farmacológico , Influenza Humana/genética , Pneumonia/tratamento farmacológico , Pneumonia/genética , Inflamação , Biologia de Sistemas , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).
Assuntos
Doenças Autoimunes , Microbioma Gastrointestinal , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Reumáticas , Humanos , Doenças Autoimunes/terapia , Doenças Reumáticas/terapia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Resultado do TratamentoRESUMO
To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-ß signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.
Assuntos
Artrite Reumatoide , Triterpenos Pentacíclicos , Triterpenos , Camundongos , Animais , Farmacologia em Rede , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Simulação de Acoplamento Molecular , Multiômica , Proteômica , Fosfatidilinositol 3-Quinases , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genéticaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Shou Tai Wan (STW), a traditional Chinese medicine formula, has been historically used for the treatment of recurrent spontaneous abortion (RSA). Despite its long-standing usage, the exact mechanism underlying the therapeutic effects of STW remains unclear in the existing literature. AIMS OF THIS STUDY: To explore the Pharmacological Mechanism of STW on RSA. METHODS: A network pharmacological methodology was utilized to predict the active compounds and potential targets of STW, collect the RSA targets and other human proteins of STW, and analyze the STW related networks. The animal experiments were also performed to validate the effect of STW on RSA. RESULTS: The results of network analysis showed that STW may regulate PI3K/AKT, MAPK, FoxO signaling pathways and so on. Animal experiment established the RSA model with CBA/J × DBA/2 mice. It was found that STW can reduce the embryo absorption rate of RSA group (p < 0.05) and balance the expression of Th 1/Th2 type cytokines compared with the model group. After 14 days of administration, the decidual and placental tissues were taken and the CD4+ T cells were isolated, and the phosphorylation level of signaling pathway was detected by Springbio720 antibody microarray. This experiment found that STW can significantly up-regulate the phosphorylation levels of STAT3 and STAT6 proteins in the STAT signaling pathway, and down-regulating the phosphorylation level of STAT1 protein. STW also significantly up-regulated the phosphorylation levels of Raf1, A-Raf, Ask1, Mek1, Mek2, JKK1, ERK1, ERK2, c-fos, c-Jun and CREB proteins in the MAPK signaling pathway, and down-regulate the phosphorylation levels of MEK6 and IKKb proteins. Compared with the RSA group, the STW group increased the expression levels of ERK1/2 mRNA and proteins and p-ERK1/2 proteins, and there was a statistical difference (p < 0.05). This is consistent with the chip results. CONCLUSION: STW may achieve therapeutic effects by interfering with the signaling pathways, biological processes and targets discovered in this study. It provides a new perspective for revealing the immunological mechanism of STW in the treatment of RSA, and also provides a theoretical basis for the clinical use of STW in the treatment of RSA.
Assuntos
Aborto Habitual , Fosfatidilinositol 3-Quinases , Camundongos , Animais , Gravidez , Feminino , Humanos , Placenta , Camundongos Endogâmicos DBA , Camundongos Endogâmicos CBA , Aborto Habitual/tratamento farmacológicoRESUMO
Objective: To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Methods: Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software. Results: A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren's syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], p = 0.003), ACR50 (RR 1.80 [1.43, 2.26], p < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], p = 0.001), DAS28 (WMD -1.11 [-1.69, -0.52], p = 0.0002), reduce ESR (WMD -11.05 [-14.58, -7.51], p < 0.00001), CRP (SMD -1.52 [-2.02, -1.02], p < 0.00001), RF (SMD -1.65 [-2.48, -0.82], p < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], p < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], p < 0.00001), BASFI score (WMD -1.07 [-1.39, -0.75], p < 0.00001), VAS (WMD -2.01 [-2.83, -1.19], p < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD -1.71 [-2.44, -0.98], p < 0.00001; IGU only group: WMD -2.10 [-2.40, -1.81], p < 0.00001) and ESSDAI score (IGU + other therapy group: WMD -1.62 [-2.30, -0.94], p < 0.00001; IGU only group: WMD -1.51 [-1.65, -1.37], p < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer's test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], p < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], p = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], p = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function. Conclusion: Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia. Systematic Review Registration: (CRD42021289489).
RESUMO
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren 's syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod's unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.
Assuntos
Antirreumáticos , Artrite Reumatoide , Síndrome de Sjogren , Humanos , Antirreumáticos/uso terapêutico , Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Cromonas/farmacologia , Síndrome de Sjogren/tratamento farmacológico , Citocinas/uso terapêuticoRESUMO
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder of the central nervous system after Alzheimer's disease. The current understanding of PD focuses mainly on the loss of dopamine neurons in the substantia nigra region of the midbrain, which is attributed to factors such as oxidative stress, alpha-synuclein aggregation, neuroinflammation, and mitochondrial dysfunction. These factors together contribute to the PD phenotype. Recent studies on PD pathology have introduced a new form of cell death known as ferroptosis. Pathological changes closely linked with ferroptosis have been seen in the brain tissues of PD patients, including alterations in iron metabolism, lipid peroxidation, and increased levels of reactive oxygen species. Preclinical research has demonstrated the neuroprotective qualities of certain iron chelators, antioxidants, Fer-1, and conditioners in Parkinson's disease. Natural plant products have shown significant potential in balancing ferroptosis-related factors and adjusting their expression levels. Therefore, it is vital to understand the mechanisms by which natural plant products inhibit ferroptosis and relieve PD symptoms. This review provides a comprehensive look at ferroptosis, its role in PD pathology, and the mechanisms underlying the therapeutic effects of natural plant products focused on ferroptosis. The insights from this review can serve as useful references for future research on novel ferroptosis inhibitors and lead compounds for PD treatment.
Assuntos
Produtos Biológicos , Ferroptose , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/metabolismo , Doenças Neurodegenerativas/metabolismo , Substância Negra/metabolismoRESUMO
BACKGROUND: Iguratimod (IGU) reduces hypergammaglobulinemia and disease activity in pSS (primary Sjögren's syndrome) patients. However, the therapeutical mechanism of IGU for pSS remains largely unknown. This study aimed to investigate the regulation of Tfh cell differentiation by IGU in pSS patients. METHODS: We prospectively enrolled 13 pSS patients treated with IGU for 3 months and examined circulating T cell and B cell subsets by flow cytometry. We measured Tfh cell differentiation treated by IGU in pSS patients and healthy controls. Transcriptome analysis combined with molecular docking were employed to identify potential therapeutical targets of IGU, which were verified by Western blot and Tfh cell differentiation. RESULTS: Tfh, plasmablast, and plasma cells were suppressed by IGU treatment at 1 and 3 months. Tfh cell differentiation and function were significant inhibited by IGU in pSS patients and healthy controls in vitro. Pyruvate dehydrogenase kinase 1 (PDK1) was identified as a target of IGU during Tfh cell differentiation, and the downstream Akt phosphorylation was attenuated by IGU. Moreover, the activity of mTORC1 and phosphorylation of STAT3 were suppressed by IGU, with downregulation of BCL6 and upregulation of PRDM1. Finally, Akt activator restored IGU-suppressed Tfh cell differentiation. CONCLUSIONS: IGU suppresses Tfh cell differentiation in pSS patients through interacting with PDK1 and suppressing Akt-mTOR-STAT3 signaling.
Assuntos
Proteínas Proto-Oncogênicas c-akt , Síndrome de Sjogren , Humanos , Simulação de Acoplamento Molecular , Síndrome de Sjogren/tratamento farmacológico , Serina-Treonina Quinases TOR , Diferenciação Celular , Fator de Transcrição STAT3RESUMO
OBJECTIVE: To evaluate efficacy and safety of total glucosides of paeony in the treatment of 5 types of inflammatory arthritis METHODS: Databases such as Pubmed, Cochran Library, Embase were searched to collect RCTs about TGP in the treatment of inflammatory arthritis. Then, the RCTs were assessed for risk of bias and RCT data were extracted. Finally, RevMan 5.4 was used for the meta-analysis. RESULTS: A total of 63 RCTs were finally included, involving 5293 participants and 5 types of types of inflammatory arthritis: rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), juvenile idiopathic arthritis (JIA), psoriatic arthritis. For AS, TGP may improve AS disease activity score (ASDAS), decrease erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF)- α and interleukin (IL)- 6; for RA, TGP may improve disease activity of 28 joints (DAS28), decrease ESR, CRP, rheumatoid factor (RF), TNF-α and IL-6; for psoriatic arthritis, TGP may improve psoriasis area and severity index (PASI) and decrease ESR; for OA, TGP may improve visual analogue scale (VAS) and decrease nitric oxide (NO); for JIA, TGP may increase total efficiency rate, decrease ESR, CRP and TNF-α. For safety, RCTs showed that the addition of TGP did not increase adverse events, and may even reduce adverse events. CONCLUSION: TGP may improve symptoms and inflammation levels in patients with inflammatory arthritis. However, due to the low quality and small number of RCTs, large-sample, multi-center clinical trials are still needed for revision or validation.
Assuntos
Artrite Psoriásica , Artrite Reumatoide , Paeonia , Humanos , Glucosídeos/efeitos adversos , Fator de Necrose Tumoral alfa , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológicoRESUMO
Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by massive loss of specific neurons. It is a progressive disabling, severe and fatal complex disease. Due to its complex pathogenesis and limitations of clinical treatment strategies, it poses a serious medical challenge and medical burden worldwide. The pathogenesis of AD is not clear, and its potential biological mechanisms include aggregation of soluble amyloid to form insoluble amyloid plaques, abnormal phosphorylation of tau protein and formation of intracellular neurofibrillary tangles (NFT), neuroinflammation, ferroptosis, oxidative stress and metal ion disorders. Among them, ferroptosis is a newly discovered programmed cell death induced by iron-dependent lipid peroxidation and reactive oxygen species. Recent studies have shown that ferroptosis is closely related to AD, but the mechanism remains unclear. It may be induced by iron metabolism, amino acid metabolism and lipid metabolism affecting the accumulation of iron ions. Some iron chelating agents (deferoxamine, deferiprone), chloroiodohydroxyquine and its derivatives, antioxidants (vitamin E, lipoic acid, selenium), chloroiodohydroxyquine and its derivatives Fer-1, tet, etc. have been shown in animal studies to be effective in AD and exert neuroprotective effects. This review summarizes the mechanism of ferroptosis in AD and the regulation of natural plant products on ferroptosis in AD, in order to provide reference information for future research on the development of ferroptosis inhibitors.
Assuntos
Doença de Alzheimer , Produtos Biológicos , Ferroptose , Animais , Doença de Alzheimer/metabolismo , Produtos Biológicos/uso terapêutico , Ferro/metabolismo , MetaisRESUMO
Objective: To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA). Methods: CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software. Results: A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events. Conclusion: Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.
Assuntos
Artrite Reumatoide , Curcumina , Hesperidina , Humanos , Resveratrol , Azeite de Oliva , Quercetina , Ensaios Clínicos Controlados Aleatórios como Assunto , Artrite Reumatoide/tratamento farmacológico , Glucosídeos , CháRESUMO
Objective: To explore the efficacy and safety of Iguratimod (IGU) intervention in the treatment of Ankylosing Spondylitis (AS). Methods: We used computer to search literature databases, collected randomized controlled trials (RCTs) related to IGU treatment of AS, and searched the relevant literature in each database until Sep. 2022. Two researchers independently carried out literature screening, data extraction, and evaluation and analysis of the risk of bias in the included studies, and then used Rev Man5.3 software for meta-analysis. The protocol is CRD42020220798. Results: A total of 10 RCTs involves in 622 patients were collected. The statistical analysis showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], P<0.00001. Quality of evidence: low), the BASFI score (WMD -1.30 [-1.48, -1.12], P<0.00001. Quality of evidence: low) and the VAS (WMD -2.01 [-2.83, -1.19], P<0.00001. Quality of evidence: very low). Meanwhile, the addition of IGU into the conventional therapy would not increase the adverse events (RR 0.65 [0.43, 0.98], P=0.04. Quality of evidence: moderate). Conclusion: IGU may be an effective and safe intervention for AS. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42020220798.
Assuntos
Espondilite Anquilosante , Humanos , Espondilite Anquilosante/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfonamidas , CromonasRESUMO
Intestinal microbiota is a unique ecosystem, known as the "second genome" of human beings. With the widespread application of next generation sequencing (NGS), especially 16 S rRNA and shotgun sequencing, numerous studies have shown that dysregulation of intestinal microbiota is associated with many central nervous system diseases. Ischemic stroke (IS) is a cerebrovascular disease with high morbidity and mortality. Brain damage in IS affects intestinal function, and intestinal dysfunction further aggravates brain damage, forming a vicious circle of mutual interference in pathology. The microbiota-gut-brain axis study based on the intestinal microbiota has opened up broader ideas for exploring its pathogenesis and risk factors, and also provided more possibilities for the selection of therapeutic targets for this type of drug. This review discussed the application of NGS technology in the study of intestinal microbiota and the research progress of microbiota-gut-brain axis in recent years, and systematically sorts out the literature on the relationship between ischemic stroke and intestinal microbiota. It starts with the characteristics of microbiota-gut-brain axis' bidirectional regulation, respectively discusses the high risk factors of IS under intestinal microbiota imbalance and the physiological and pathological changes of intestinal microbiota after IS, and summarizes the related targets, in order to provide reliable reference for the treatment of IS from intestinal microbiota. In addition, natural botanical active ingredients have achieved good results in the treatment of IS based on regulating the homeostasis of gut microbiota, providing new evidence for studying the potential targets and therapies of IS based on the microbiota-gut-brain axis.